The objective of this clinical proposal is to identify the optimal source of hematopoietic stem cell rescue following high-dose chemotherapy given for non-Hodgkin's lymphoma (NHL). In a preliminary non-randomized clinical study, patients with intermediate grade NHL who received an autologous bone marrow transplant (ABNT) (N=105) had a three year event- free survival (EFS) of 24%. This compared to a three year EFS of 38% in patients with intrinsic bone marrow abnormalities who underwent high-dose therapy with peripheral stem cell transplantation (PSCT) (N=53) (1). The clinical trial in this proposal will randomize patients with intermediate grade or immunoblastic NHL to receive high-dose chemotherapy with hematopoietic reconstitution with either ABMT or PSCT. All patients will have histologically negative bone marrow and will be stratified before randomization by other recognized prognostic factors. The two companion laboratory studies will evaluate possible mechanisms to explain differences in outcome observed between the patients receiving an autologous bone marrow or a peripheral stem cell transplant. One study will evaluate the presence of occult tumor cells as minimal residual disease in the graft by in-vitro tumor culture assays and molecular biologic techniques. The other laboratory study will evaluate phenotype of cells within the hematopoietic graft given back to the patient, as well as the re-appearance of immuno-competent cells in the patients post- transplant, including natural killer cell and leukocyte activated killer cell activity, cell phenotype by flow cytometric analysis, as well as functional analysis. The findings in the laboratory studies will be correlated to the survival and event-free survival in the patients receiving high-dose chemotherapy with ABMT or PSCT.